Natural and artificial RNAs occupy the same restricted region of sequence space
- Ryan Kennedy1,
- Manuel E. Lladser2,
- Zhiyuan Wu3,
- Chen Zhang4,
- Michael Yarus5,
- Hans De Sterck3 and
- Rob Knight6,7
- 1Department of Computer Science, University of Colorado, Boulder, Colorado 80309, USA
- 2Department of Applied Mathematics, University of Colorado, Boulder, Colorado 80309, USA
- 3Department of Applied Mathematics, University of Waterloo, Ontario N2L 3G1, Canada
- 4David R. Cheriton School of Computer Science, University of Waterloo, Ontario N2L 3G1, Canada
- 5Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, Colorado 80309, USA
- 6Department of Chemistry and Biochemistry, University of Colorado, Boulder, Colorado 80309, USA
- 7Howard Hughes Medical Institute, Chevy Chase, Maryland 20815, USA
Abstract
Different chemical and mutational processes within genomes give rise to sequences with different compositions and perhaps different capacities for evolution. The evolution of functional RNAs may occur on a “neutral network” in which sequences with any given function can easily mutate to sequences with any other. This neutral network hypothesis is more likely if there is a particular region of composition that contains sequences that are functional in general, and if many different functions are possible within this preferred region of composition. We show that sequence preferences in active sites recovered by in vitro selection combine with biophysical folding rules to support the neutral network hypothesis. These simple active-site specifications and folding preferences obtained by artificial selection experiments recapture the previously observed purine bias and specific spread along the GC axis of naturally occurring aptamers and ribozymes isolated from organisms, although other types of RNAs, such as miRNA precursors and spliceosomal RNAs, that act primarily through complementarity to other amino acids do not share these preferences. These universal evolved sequence features are therefore intrinsic in RNA molecules that bind small-molecule targets or catalyze reactions.
Keywords
Footnotes
-
Reprint requests to: Rob Knight, Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO 80309, USA; e-mail: rob{at}spot.colorado.edu; fax: (303) 492-7744.
-
Article published online ahead of print. Article and publication date are at http://www.rnajournal.org/cgi/doi/10.1261/rna.1923210.
-
- Received September 10, 2009.
- Accepted October 19, 2009.
- Copyright © 2010 RNA Society
